Monitoring blood glucose levels regularly is very important in proper diabetes management, especially for children with type I diabetes. The conventional glucose sensor technologies have limited the development of glucose sensors, especially in its measurements of blood glucose in the hypoglycemia range (see reference 23). The third generation glucose sensors based on DET phenomena were widely reported (see references 6-8). The third generation biosensors for direct glucose measurements are based on an intriguing phenomenon known for the last decade as the bioelectrocatalysis with the direct electron transfer (DET) between the electrode and the redox active sites of bio molecules (see references 1-5). Direct measurement of analyte without using mediators is one the advantages that this type of sensors offer, because the mediators are leachable from the polymer network and are toxic.
Nano-structured material used for developing novel sensors have been reported in the last decade. Colloidal nano gold particles have been extensively studied for the utility of promoting DET between enzymes and the nano particles (see references 9-10). Joseph Wang had extensive review articles in this field (see references 11-12). The carbon nanotube modified glucose oxidase (GOD) enzyme electrode capable of promoting electron transfer is reviewed in his articles. Vaseashta and Irudayaraj have a review paper on nanostructured sensors (see reference 13).
Nanowire and nanopore based sensors have drawn great interest recently because they are extremely sensitive and well suited for multiple target detection, which overcame the disadvantages of previous technology. However, as the reviewers Vaseashta and Irudayaraj point out, the technology is still in the development stage and the robustness has not been established (see reference 13). It has been shown that the nanopores played an important role in enabling multiple step reactions with higher reaction rate in comparison with the same system immobilized on polystyrene without nanopores (see reference 14).
Cylcodextrins (CD) existing in nature consists of 6 to 12 glucose units. The shapes of cyclodextrins are like donuts, or a truncated conical basket. These CDs have an internal hydrophobic property and external hydrophilic property. The internal pore diameter is 0.78 nm for β-CD, and its height is 0.78 nm. In the reports on recent development in this field, biosensors were developed utilizing the unique properties of CDs to form nanopores or nanotubes with polymers and biological materials (see references 17-22) to detect various toxic substances which are undetectable by conventional sensors.
As indicated above, however, robust nanopore structured sensors have yet to be reported. Therefore, there is a need for a biosensor for accurate glucose measurement, especially in the hypoglycemia range. In addition, there is a need for biosensors that do not utilize a mediator. These and other needs have been met by the present invention.